{"gene":"ATP9B","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2011,"finding":"ATP9B localizes exclusively to the trans-Golgi network (TGN) and is able to exit the ER independently of CDC50 proteins, unlike most other P4-ATPases. RNAi depletion of CDC50 proteins did not prevent ATP9B ER exit or TGN localization.","method":"RNAi depletion of CDC50 proteins, fluorescence microscopy, subcellular fractionation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct loss-of-function (RNAi) with clear subcellular localization readout, replicated across multiple P4-ATPase family members in same study","pmids":["21914794"],"is_preprint":false},{"year":2011,"finding":"The N-terminal cytoplasmic region of ATP9B contains a Golgi (TGN) localization signal. A chimeric ATP9 protein in which the N-terminal cytoplasmic region of ATP9A was replaced with the corresponding region of ATP9B localized exclusively to the Golgi.","method":"Chimeric protein construction and fluorescence microscopy","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain-swap chimera experiment with clear localization readout, single lab","pmids":["21914794"],"is_preprint":false},{"year":2025,"finding":"ATP9A and ATP9B form homomeric and/or heteromeric complexes and together contribute to the exocytic pathway, transporting VSVG from the Golgi to the plasma membrane. The flippase activities of both ATP9A and ATP9B are required for this transport process. Formation of the heteromeric complex contributes to retention of ATP9A in the Golgi.","method":"Co-immunoprecipitation (complex formation), VSVG transport assay, flippase activity assays, loss-of-function knockdown","journal":"Life science alliance","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification, functional transport assay, flippase activity measurement, and localization data reported in a single study with multiple orthogonal methods; preprint version also available","pmids":["40234049"],"is_preprint":false},{"year":2024,"finding":"ATP9A and ATP9B form homomeric and/or heteromeric complexes; heteromeric complex formation contributes to retention of ATP9A in the Golgi. Both ATP9A and ATP9B flippase activities are required for VSVG transport from the Golgi to the plasma membrane in the secretory pathway.","method":"Co-immunoprecipitation, VSVG secretory transport assay, flippase activity assay, fluorescence microscopy","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — preprint with multiple orthogonal methods (Co-IP, transport assay, flippase activity), single lab, not yet peer-reviewed","pmids":[],"is_preprint":true},{"year":2025,"finding":"ATP9A (the close paralog of ATP9B) functions as a monomeric P4-ATPase flippase that does not require the CDC50 auxiliary subunit. Its outward gating is achieved by movement of TM6-10 helices (initiated by unwinding of TM6), distinct from canonical P-type ATPase gating involving TM1-2/A domain movement. ATPase activity is significantly stimulated by negatively charged phospholipids (phosphatidylserine, phosphatidylinositol, and phosphorylated PI species). This gating mechanism is proposed to be shared by ATP9B as both belong to the P4B-type subclass.","method":"Cryo-EM structure at 2.2 Å resolution, ATPase activity assays with various phospholipids, molecular dynamics simulation","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution cryo-EM structure with functional ATPase assays, but findings are directly about ATP9A; ATP9B is mentioned as sharing the same P4B-type mechanism by inference, not direct experiment","pmids":["40876594"],"is_preprint":false}],"current_model":"ATP9B is a P4-ATPase lipid flippase that localizes exclusively to the trans-Golgi network (TGN) via a Golgi targeting signal in its N-terminal cytoplasmic region, exits the ER independently of CDC50 auxiliary proteins, forms homomeric and/or heteromeric complexes with its paralog ATP9A, and together with ATP9A uses its flippase activity to facilitate transport of cargo (e.g., VSVG) from the Golgi to the plasma membrane in the exocytic pathway."},"narrative":{"mechanistic_narrative":"ATP9B is a P4-ATPase lipid flippase that operates in the exocytic pathway of the trans-Golgi network (TGN) [PMID:21914794, PMID:40234049]. Unlike most P4-ATPases, ATP9B exits the endoplasmic reticulum and reaches the TGN independently of CDC50 auxiliary subunits, and its restricted TGN localization is conferred by a targeting signal in its N-terminal cytoplasmic region [PMID:21914794]. ATP9B forms homomeric and/or heteromeric complexes with its paralog ATP9A, and this heteromeric association helps retain ATP9A in the Golgi; the flippase activities of both proteins are jointly required to transport cargo such as VSVG from the Golgi to the plasma membrane [PMID:40234049]. Beyond its role in lipid flipping and Golgi-to-plasma-membrane cargo transport, no further substrate specificity or physiological context for ATP9B has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Established where ATP9B resides and how it gets there, distinguishing it from the broader P4-ATPase family that depends on CDC50 chaperones for ER exit.","evidence":"RNAi depletion of CDC50 proteins with fluorescence microscopy and subcellular fractionation in cultured cells","pmids":["21914794"],"confidence":"High","gaps":["Does not define ATP9B's transported lipid substrate","Does not explain how ATP9B exits the ER without a CDC50 partner"]},{"year":2011,"claim":"Localized the TGN-targeting determinant to the N-terminal cytoplasmic region, explaining the molecular basis for ATP9B's exclusive Golgi distribution.","evidence":"ATP9A/ATP9B chimeric domain-swap constructs assessed by fluorescence microscopy","pmids":["21914794"],"confidence":"Medium","gaps":["The specific sequence motif and any recognizing trafficking machinery are not identified","Single-lab chimera result without orthogonal validation"]},{"year":2024,"claim":"First evidence that ATP9B partners with ATP9A and that their combined flippase activity drives Golgi-to-plasma-membrane cargo transport (preprint).","evidence":"Co-immunoprecipitation, VSVG secretory transport assay, flippase activity assay, fluorescence microscopy (bioRxiv preprint)","pmids":[],"confidence":"Medium","gaps":["Preprint, not yet peer-reviewed","Stoichiometry and structural basis of the ATP9A/ATP9B complex unresolved"]},{"year":2025,"claim":"Confirmed the ATP9A/ATP9B complex and showed that both flippase activities are required for VSVG exocytic transport, with heteromeric assembly controlling ATP9A Golgi retention.","evidence":"Reciprocal Co-immunoprecipitation, VSVG transport assay, flippase activity assays, and knockdown loss-of-function in cultured cells","pmids":["40234049"],"confidence":"High","gaps":["The lipid species flipped by ATP9B in this process is not defined","Whether ATP9B can function independently of ATP9A is unclear","No structural model of ATP9B itself"]},{"year":2025,"claim":"Defined a non-canonical P4B-type gating mechanism and phospholipid-stimulated ATPase activity for the close paralog ATP9A, inferred to extend to ATP9B.","evidence":"2.2 Å cryo-EM structure of ATP9A, ATPase assays with various phospholipids, and molecular dynamics simulation","pmids":["40876594"],"confidence":"Medium","gaps":["Mechanism is demonstrated for ATP9A; ATP9B is included only by family inference, not direct experiment","No experimental ATP9B structure or substrate specificity data"]},{"year":null,"claim":"The specific lipid substrate(s) of ATP9B, its independent (ATP9A-free) function, and its physiological/organismal role remain undefined.","evidence":"No direct evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No ATP9B substrate identified","No experimental ATP9B structure","No in vivo or disease-linked phenotype reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2]}],"complexes":["ATP9A-ATP9B heteromeric flippase complex"],"partners":["ATP9A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O43861","full_name":"Probable phospholipid-transporting ATPase IIB","aliases":["ATPase class II type 9B"],"length_aa":1147,"mass_kda":129.3,"function":"","subcellular_location":"Golgi apparatus, trans-Golgi network membrane","url":"https://www.uniprot.org/uniprotkb/O43861/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ATP9B","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ATP9B","total_profiled":1310},"omim":[{"mim_id":"619791","title":"ATPase, PHOSPHOLIPID-TRANSPORTING, 10B; ATP10B","url":"https://www.omim.org/entry/619791"},{"mim_id":"614446","title":"ATPase, CLASS II, TYPE 9B; ATP9B","url":"https://www.omim.org/entry/614446"},{"mim_id":"191327","title":"UBIQUINOL-CYTOCHROME c REDUCTASE, RIESKE IRON-SULFUR; UQCRFS1","url":"https://www.omim.org/entry/191327"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ATP9B"},"hgnc":{"alias_symbol":["ATPIIB"],"prev_symbol":[]},"alphafold":{"accession":"O43861","domains":[{"cath_id":"2.70.150.10","chopping":"233-363","consensus_level":"medium","plddt":85.1547,"start":233,"end":363},{"cath_id":"-","chopping":"422-441_938-1147","consensus_level":"high","plddt":84.3049,"start":422,"end":1147},{"cath_id":"3.40.50.1000","chopping":"465-474_746-908","consensus_level":"high","plddt":87.6567,"start":465,"end":908},{"cath_id":"3.40.1110.10","chopping":"481-508_538-558_581-742","consensus_level":"high","plddt":87.0938,"start":481,"end":742}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43861","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43861-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43861-F1-predicted_aligned_error_v6.png","plddt_mean":79.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ATP9B","jax_strain_url":"https://www.jax.org/strain/search?query=ATP9B"},"sequence":{"accession":"O43861","fasta_url":"https://rest.uniprot.org/uniprotkb/O43861.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43861/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43861"}},"corpus_meta":[{"pmid":"21914794","id":"PMC_21914794","title":"ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes to the trans-Golgi network in a CDC50 protein-independent manner.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21914794","citation_count":110,"is_preprint":false},{"pmid":"29305974","id":"PMC_29305974","title":"Circular RNA Atp9b, a competing endogenous RNA, regulates the progression of osteoarthritis by targeting miR-138-5p.","date":"2018","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/29305974","citation_count":87,"is_preprint":false},{"pmid":"24092497","id":"PMC_24092497","title":"Establishing a reference group for distal 18q-: clinical description and molecular basis.","date":"2013","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24092497","citation_count":25,"is_preprint":false},{"pmid":"16434434","id":"PMC_16434434","title":"An alloplasmic male-sterile line of Brassica oleracea harboring the mitochondria from Diplotaxis muralis expresses a novel chimeric open reading frame, orf72.","date":"2006","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16434434","citation_count":17,"is_preprint":false},{"pmid":"31735661","id":"PMC_31735661","title":"circAtp9b knockdown alleviates LPS-caused inflammation provided that microRNA-27a is upregulated.","date":"2019","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/31735661","citation_count":13,"is_preprint":false},{"pmid":"26625115","id":"PMC_26625115","title":"Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26625115","citation_count":11,"is_preprint":false},{"pmid":"34392169","id":"PMC_34392169","title":"Identification of novel candidate genes for age at first calving in Nellore cows using a SNP chip specifically developed for Bos taurus indicus cattle.","date":"2021","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/34392169","citation_count":11,"is_preprint":false},{"pmid":"34675997","id":"PMC_34675997","title":"Overexpression of circAtp9b in ulcerative colitis is induced by lipopolysaccharides and upregulates PTEN to promote the apoptosis of colonic epithelial cells.","date":"2021","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34675997","citation_count":7,"is_preprint":false},{"pmid":"40234049","id":"PMC_40234049","title":"Lipid flippases ATP9A and ATP9B form a complex and contribute to the exocytic pathway from the Golgi.","date":"2025","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/40234049","citation_count":5,"is_preprint":false},{"pmid":"25837627","id":"PMC_25837627","title":"A family with atypical Hailey Hailey disease--is there more to the underlying genetics than ATP2C1?","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25837627","citation_count":4,"is_preprint":false},{"pmid":"38968866","id":"PMC_38968866","title":"Identification of candidate genes associated with primary feathers of tianfu nonghua ducks based on Genome-wide association studies.","date":"2024","source":"Poultry science","url":"https://pubmed.ncbi.nlm.nih.gov/38968866","citation_count":2,"is_preprint":false},{"pmid":"41001506","id":"PMC_41001506","title":"Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.","date":"2025","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41001506","citation_count":1,"is_preprint":false},{"pmid":"40876594","id":"PMC_40876594","title":"A unique gating mechanism revealed by the cryo-EM structure of monomeric ATP9A flippase.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40876594","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.11.13.623339","title":"Lipid flippases ATP9A and ATP9B form a complex and contribute to the secretory pathway from the Golgi apparatus","date":"2024-11-15","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.13.623339","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9448,"output_tokens":1333,"usd":0.02417,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7982,"output_tokens":1912,"usd":0.043855,"stage2_stop_reason":"end_turn"},"total_usd":0.068025,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"ATP9B localizes exclusively to the trans-Golgi network (TGN) and is able to exit the ER independently of CDC50 proteins, unlike most other P4-ATPases. RNAi depletion of CDC50 proteins did not prevent ATP9B ER exit or TGN localization.\",\n      \"method\": \"RNAi depletion of CDC50 proteins, fluorescence microscopy, subcellular fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct loss-of-function (RNAi) with clear subcellular localization readout, replicated across multiple P4-ATPase family members in same study\",\n      \"pmids\": [\"21914794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The N-terminal cytoplasmic region of ATP9B contains a Golgi (TGN) localization signal. A chimeric ATP9 protein in which the N-terminal cytoplasmic region of ATP9A was replaced with the corresponding region of ATP9B localized exclusively to the Golgi.\",\n      \"method\": \"Chimeric protein construction and fluorescence microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain-swap chimera experiment with clear localization readout, single lab\",\n      \"pmids\": [\"21914794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ATP9A and ATP9B form homomeric and/or heteromeric complexes and together contribute to the exocytic pathway, transporting VSVG from the Golgi to the plasma membrane. The flippase activities of both ATP9A and ATP9B are required for this transport process. Formation of the heteromeric complex contributes to retention of ATP9A in the Golgi.\",\n      \"method\": \"Co-immunoprecipitation (complex formation), VSVG transport assay, flippase activity assays, loss-of-function knockdown\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification, functional transport assay, flippase activity measurement, and localization data reported in a single study with multiple orthogonal methods; preprint version also available\",\n      \"pmids\": [\"40234049\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ATP9A and ATP9B form homomeric and/or heteromeric complexes; heteromeric complex formation contributes to retention of ATP9A in the Golgi. Both ATP9A and ATP9B flippase activities are required for VSVG transport from the Golgi to the plasma membrane in the secretory pathway.\",\n      \"method\": \"Co-immunoprecipitation, VSVG secretory transport assay, flippase activity assay, fluorescence microscopy\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — preprint with multiple orthogonal methods (Co-IP, transport assay, flippase activity), single lab, not yet peer-reviewed\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ATP9A (the close paralog of ATP9B) functions as a monomeric P4-ATPase flippase that does not require the CDC50 auxiliary subunit. Its outward gating is achieved by movement of TM6-10 helices (initiated by unwinding of TM6), distinct from canonical P-type ATPase gating involving TM1-2/A domain movement. ATPase activity is significantly stimulated by negatively charged phospholipids (phosphatidylserine, phosphatidylinositol, and phosphorylated PI species). This gating mechanism is proposed to be shared by ATP9B as both belong to the P4B-type subclass.\",\n      \"method\": \"Cryo-EM structure at 2.2 Å resolution, ATPase activity assays with various phospholipids, molecular dynamics simulation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution cryo-EM structure with functional ATPase assays, but findings are directly about ATP9A; ATP9B is mentioned as sharing the same P4B-type mechanism by inference, not direct experiment\",\n      \"pmids\": [\"40876594\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ATP9B is a P4-ATPase lipid flippase that localizes exclusively to the trans-Golgi network (TGN) via a Golgi targeting signal in its N-terminal cytoplasmic region, exits the ER independently of CDC50 auxiliary proteins, forms homomeric and/or heteromeric complexes with its paralog ATP9A, and together with ATP9A uses its flippase activity to facilitate transport of cargo (e.g., VSVG) from the Golgi to the plasma membrane in the exocytic pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ATP9B is a P4-ATPase lipid flippase that operates in the exocytic pathway of the trans-Golgi network (TGN) [#0, #2]. Unlike most P4-ATPases, ATP9B exits the endoplasmic reticulum and reaches the TGN independently of CDC50 auxiliary subunits, and its restricted TGN localization is conferred by a targeting signal in its N-terminal cytoplasmic region [#0, #1]. ATP9B forms homomeric and/or heteromeric complexes with its paralog ATP9A, and this heteromeric association helps retain ATP9A in the Golgi; the flippase activities of both proteins are jointly required to transport cargo such as VSVG from the Golgi to the plasma membrane [#2]. Beyond its role in lipid flipping and Golgi-to-plasma-membrane cargo transport, no further substrate specificity or physiological context for ATP9B has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established where ATP9B resides and how it gets there, distinguishing it from the broader P4-ATPase family that depends on CDC50 chaperones for ER exit.\",\n      \"evidence\": \"RNAi depletion of CDC50 proteins with fluorescence microscopy and subcellular fractionation in cultured cells\",\n      \"pmids\": [\"21914794\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define ATP9B's transported lipid substrate\", \"Does not explain how ATP9B exits the ER without a CDC50 partner\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Localized the TGN-targeting determinant to the N-terminal cytoplasmic region, explaining the molecular basis for ATP9B's exclusive Golgi distribution.\",\n      \"evidence\": \"ATP9A/ATP9B chimeric domain-swap constructs assessed by fluorescence microscopy\",\n      \"pmids\": [\"21914794\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The specific sequence motif and any recognizing trafficking machinery are not identified\", \"Single-lab chimera result without orthogonal validation\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"First evidence that ATP9B partners with ATP9A and that their combined flippase activity drives Golgi-to-plasma-membrane cargo transport (preprint).\",\n      \"evidence\": \"Co-immunoprecipitation, VSVG secretory transport assay, flippase activity assay, fluorescence microscopy (bioRxiv preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not yet peer-reviewed\", \"Stoichiometry and structural basis of the ATP9A/ATP9B complex unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Confirmed the ATP9A/ATP9B complex and showed that both flippase activities are required for VSVG exocytic transport, with heteromeric assembly controlling ATP9A Golgi retention.\",\n      \"evidence\": \"Reciprocal Co-immunoprecipitation, VSVG transport assay, flippase activity assays, and knockdown loss-of-function in cultured cells\",\n      \"pmids\": [\"40234049\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The lipid species flipped by ATP9B in this process is not defined\", \"Whether ATP9B can function independently of ATP9A is unclear\", \"No structural model of ATP9B itself\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a non-canonical P4B-type gating mechanism and phospholipid-stimulated ATPase activity for the close paralog ATP9A, inferred to extend to ATP9B.\",\n      \"evidence\": \"2.2 Å cryo-EM structure of ATP9A, ATPase assays with various phospholipids, and molecular dynamics simulation\",\n      \"pmids\": [\"40876594\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism is demonstrated for ATP9A; ATP9B is included only by family inference, not direct experiment\", \"No experimental ATP9B structure or substrate specificity data\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific lipid substrate(s) of ATP9B, its independent (ATP9A-free) function, and its physiological/organismal role remain undefined.\",\n      \"evidence\": \"No direct evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No ATP9B substrate identified\", \"No experimental ATP9B structure\", \"No in vivo or disease-linked phenotype reported\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140359\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"ATP9A-ATP9B heteromeric flippase complex\"],\n    \"partners\": [\"ATP9A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}